Patent GB-788914-A (GB)
Title: Improvements in or relating to diquaternary compounds
Inventor: ADAMSON DONALD WALLACE
IPC: C07D295/13
Filed: 1954-02-25
Abstract: The invention comprises compounds of the general formula <FORM:0788914/IV (b)/1> wherein R1 and R2 are the same or different and are each a cycloalkyl group (for example a cyclohexyl group), or a phenyl group which may carry one or more substituents, said substituents being halogen atoms (for example chlorine or bromine atoms), phenyl or lower alkyl groups (having from 1 to 4 carbon atoms) or lower alkoxy groups (having from one to four carbon atoms), the total number of carbon atoms in the alkyl and/or alkoxy groups present on either of the phenyl groups not exceeding four; n is an integer from 1 to 9; +N1 is a quaternary nitrogen atom either carrying two alkyl groups having together up to five carbon atoms, preferably two or three carbon atoms, or forming part of a pyrrolidino, piperidino or morpholino ring; +N2 is a quaternary nitrogen atom carrying at least one alkyl group having from 1 to 4 carbon atoms and either carrying two further alkyl groups giving a total of up to 9 carbon atoms, preferably a total of 3 to 6 carbon atoms, or forming part of a pyrrolidino, piperidino or morpholino ring; Y is an alkylene chain having from 2 to 10 carbon atoms, preferably 2 to 6 carbon atoms, or +N1-Y- + N2 may be a piperazine ring in which + N1 is a quaternary nitrogen atom carrying one alkyl group having up to 4 carbon atoms and +N2 is a quaternary nitrogen atom carrying two alkyl groups having a total of up to 4 carbon atoms, the total number of carbon atoms in the alkyl groups not exceeding 6; and A- is an anion of an inorganic or organic acid which may be, for example, halide or alkyl sulphate.  Such compounds may be obtained by heating with a quaternizing agent the corresponding base of the formula <FORM:0788914/IV (b)/2> in which N3 is a secondary, tertiary or quaternary nitrogen atom and N4 is a primary or tertiary or quaternary nitrogen atom when N3 is a secondary or tertiary nitrogen atom or a primary or tertiary nitrogen atom when N3 is a quaternary nitrogen atom.  The products (with the exception of the piperazine compounds) can also be prepared by reacting a compound of the formula Z-Y-N2-A- with a compound of the formula R1R2C(OH)CH2(CH2)nN5, where N5 is a tertiary nitrogen atom. Compounds of formula II are obtainable by reacting a halogeno ester of the formula (III) R3O2C.CH2(CH2)n.Z (where R3 may be alkyl) with a diamine of the formula HN5-Y-N4, where N5 is a nitrogen atom carrying one alkyl group having up to 4 carbon atoms, the product obtained of formula R3O2C.CH2(CH2) n.N5-Y-N4 being either reacted with excess of a compound such as R1MgZ or R1Li (to give a carbinol II in which R1 and R2 are alike) or (where R1 and R2 are different) with about two molecular proportions of Grignard reagent to give a ketone R1.CO.CH2(CH2)n.N5-Y-N4 which is then reacted with R2Li or R2MgZ. Alternatively a halogeno compound of the formula R1R2C(OH)-CH2(CH2)nZ is reacted with the diamine NH5-Y-N4.  Compounds of formula II, where R1 and/or R2 are cyclohexyl, may be obtained by hydrogenation of the corresponding phenyl derivatives.  If N4 is a primary nitrogen atom the nitrile of the formula R1R2C(OH)-CH2(CH2) nNR4(CH2)mCN, where R4 is an alkyl group and m is an integer from 2 to 9 (from the reaction of R1R2C(OH)CH2(CH2)nNHR4 and Z(CH2)mCN) may be reduced to the compound of formula II.  Equations for similar reactions, where N3 is a secondary or quaternary nitrogen atom, respectively, are also given.  Compounds of formula II can also be prepared by reaction of compounds of the formul  R1R2C(OH)(CH2)-(CH2)nBr and either H2N(CH2)qNR6R7 or H2N(CH2)q+NR6R7R8A, where q is an integer from 2 to 10 and R6 and R7 are either each alkyl groups having a total of up to eight carbon atoms or NR6R7 is a pyrrolidino, piperidino or morpholino ring and R8 is an alkyl group.  Compounds of formula II in which N3 is a quaternary nitrogen atom and N4 is a tertiary nitrogen atom can be prepared by reacting compounds of the formula <FORM:0788914/IV (b)/3> where X is C.OH.CH2, with compounds of the formula HNR6R7.  In Example (1) N1-(3-hydroxy - 3 : 3 - diphenylporpyl) - N1 : N2 : N2 - trimethyl-piperazinium diiodide is prepared by quaternation of the corresponding base by reaction with methyl iodide.  Similarly prepared are (2) N2 : N2-diethyl-N1-(3-hydroxy-3 : 3 - diphenylpropyl) - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium diiodide; (3) N1 - (3 - hydroxy - 3 : 3 - diphenylpropyl) - N1 : N1 : N2 - trimethylethylene - 1 - ammonium-2-pyrrolidinium diiodide; (4) N1-(3-hydroxy-3 : 3 - diphenylpropyl) - N1 : N1 : N2 - trimethylethylene - 1 - ammonium - 2 - piperidinium diiodide; (5) N1 - (3 - hydroxy - 3 : 3 - diphenylpropyl) - N1 : N1 : N2 - trimethylethylene - 1 - ammonium - 2 - morpholinium diiodide; (6) N2 : N2 - diethyl - N1 - (4 - hydroxy - 4 : 4 - diphenylbutyl) - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium diiodide; (7) N2 : N2 - diethyl - N1 - (5 - hydroxy - 5 : 5 - diphenylpentyl) - N1 : N1 : N1 - trimethylethylene - 1 : 2 - diammonium diiodide; (8) N1-(6-hydroxy-6 : 6-diphenylhexyl) - N1 : N2 : N2 - trimethylpiperazinium diiodide; (9) N2 : N2-diethyl-N1-(6-hydroxy - 6 : 6 - diphenylhexyl) - N1 : N1 : N2 - trimethylethylen - 1 : 2 - diammonium diiodide; (10) N1 - (6 - hydroxy - 6 : 6 - diphenylhexyl) - N1 : N1 : N2 - trimethylethylene - 1 - ammonium - 2 - piperidinium diiodide; (11) N1 - (6 - hydroxy - 6 : 6 - diphenylhexyl) - N1 : N1 : N2 - trimethylethylene - 1 - ammonium-2-morpholinium diiodide; (12) N1-ethyl-N1-(6-hydroxy - 6 : 6 - diphenylhexyl) - N1 : N2 - dimethylethylene - 1 - ammonium - 2 - morpholinium diiodide; (13) N2 : N2 - di - n - butyl - N1 - (6 - hydroxy - 6 : 6 - diphenylhexyl) - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium diiodide; (14) N2 : N2-diethyl-N1-(7 - hydroxy - 7 : 7 - diphenylheptyl) - N1 : N1 : N2-trimethylethylene - 1 : 2 - diammonium diiodide; (15) N2 : N2-diethyl-N1-(9-hydroxy-9 : 9-diphenylnonyl) - N1 : N1 : N2 - trimethylethylene-1 : 2-diammonium diiodide; (16) N2 : N2-diethyl - N1 - (11 - hydroxy - 11 : 11 - diphenylundecyl) - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium diiodide; N2 : N2 - diethyl - N1 - [3 - hydroxy - 3 : 3 - di - (4 - methylphenyl) propyl] - - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium diiodide; (18) N2 : N2-diethyl-N1-[5 - hydroxy - 5 - (4 - methylphenyl) - 5 - phenylpentyl] - - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium diiodide; (19) N2 : N2 - diethyl - N1 - [6 - hydroxy - 6 - (4 - methylphenyl) - 6 - phenylhexyl] - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium diiodide; (20) N2 : N2 - diethyl - N1 - [6 - hydroxy - 6 : 6 - di - (2 - methylphenyl) hexyl] - N1 : N1 : N2 - trimethylethylene-1 : 2 - diammonium diiodide; (21) N2 : N2-diethyl - N1 - [6 - hydroxy - 6 : 6 - di - (3 - methylphenyl) hexyl]- N1 : N1 : N2 - trimethylethylene-1 : 2 - diammonium diiodide; (22) N2 : N2-diethyl - N1 - [6 - hydroxy - 6 : 6 - di - (4 - methylphenyl) - hexyl] - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium diiodide; (23) N2 : N2 - diethyl - N1 - [6 - hydroxy - 6 : 6 - bis(2 : 5 - dimethylphenyl) hexyl] - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium diiodide; (24) N1 - [6 : 6 - di - (4 - tert. - butylphenyl) - 6 - hydroxyhexyl] - N2 : N2 - diethyl - N1 : N1 : N2 - trimethylethylene-1 : 2-diammonium diiodide; (25) N1 - [6 : 6 - di - (4 - chlorophenyl) - 6 - hydroxyhexyl] - N2 : N2 - diethyl - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium diiodide; (26) N2 : N2 - diethyl - N1 - [6 - hydroxy-6 : 6-di-(4-methoxyphenyl) hexyl]- N1 : N1 : N2-trimethylethylene-1 : 2-diammonium diiodide; (27) N1 - [3 - hydroxy - 3 - (4 - diphenyl) - 3 - phenylpropyl] - - N1 : N1 : N2 - trimethylethylene-1 - ammonium - 2 - morpholinium diiodide; (28) N2 : N2 - diethyl - N1 - (6 - cyclohexyl - 6 - hydroxy - - 6 - phenylhexyl) - N1 : N1 : N2 - trimethylethylethylene - 1 : 2 - diammonium diiodide; (29) N2 : N2-diethyl-N1-(6 : 6-dicyclohexyl - 6 - hydroxyhexyl) - - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium diiodide; (30) N1 - (6 : 6 - dicyclohexyl - 6 - hydroxyhexyl) - N1 : N1 : N2 - trimethylethylene - 1 - ammonium-2-morpholinium diiodide; (31) N1-(6 - hydroxy - 6 : 6 - diphenylhexyl - N2 : N2 : N2-trimethyl - trimethylene - 3 - ammonium - 1 - pyrrolidinium diiodide.  Specifications 682,160 and 788,915 are referred to.